The active adhesive dressing (AAD) contracts when it heats up to body temperature, allowing it to accelerate the healing of open wounds on the skin. It could also be used to close wounds on internal tissues such as the heart, deliver drugs, and function in soft robotics-based therapies. Credit: Wyss Institute at Harvard University

Embryo-inspired dressings can speed up wound healing

At some stage in our lives, we all have experienced skin wounds. Minor wounds can be healed by treating with antiseptic and covering with sterile dressing and bandages. Bandage maintains it moist, limit pain, and decrease exposure to harmful microbes, but do not actively help in the wound healing.

In recent years, scientists have developed more advanced wound dressings have that can track healing elements such as pH and temperature and offer therapies to a wound site, but are complicated to produce, costly, and hard to personalize, restricting their potential for common use.

To improve things, a collaborative team of researchers has developed a scalable technique to accelerate wound healing which is based on heat-responsive hydrogels. Named as active adhesive dressings (AADs), can close injuries considerably quicker than other techniques and stop the growth of bacteria without any extra devices or stimuli.

“This technology has the potential to be used not only for skin injuries, but also for chronic wounds like diabetic ulcers and pressure sores, for drug delivery, and as components of soft robotics-based therapies,” said corresponding author David Mooney, Ph.D., a Founding Core Faculty member of the Wyss Institute.

AADs are the result of inspiration from the embryo development process, as the skin of embryo can repair itself entirely without the formation of scar tissue. To do this, the embryonic skin cells generate fibers made up of the actin protein around a wound. This fibers contract to pull together the edges of the wound, like a closed drawstring bag. After a certain fetus development stage, skin cells lose this potential and any wounds that happen after that stage during the healing trigger inflammation and scarring.

To imitate the skin repair mechanism of embryo stage, researchers modified the previously developed adhesive hydrogels by adding a thermoresponsive polymer known as PNIPAm, which repels water as well as shrinks at around 90° F. On being exposed to body temperature, contraction begins in the resulting hybrid hydrogel, which then transmits the contraction force of PNIPAm component into underlying tissues by forming a strong bond between the tissue and hydrogel alginate.

“The AAD bonded to pig skin with over ten times the adhesive force of a Band-AidⓇ and prevented bacteria from growing, so this technology is already significantly better than most commonly used wound protection products, even before considering its wound-closing properties,” said Benjamin Freedman, Ph.D., a Postdoctoral Fellow who is leading the project.

Researchers tested this newly developed wound dressing on mouse skin patches and observed about 45% decrease in wound area as compared to untreated samples. Interestingly these active adhesive dressings (AADs) sealed wounds quicker than other conventional treatments like microgels and other hydrogel kinds. Also, no inflammation or immune responses were reported, suggesting that it is safe to use on living tissues.

In addition, researchers added different amounts of acrylamide monomers during the manufacturing process, to tweak the amount of wound closure carried by the AAD.

“This property could be useful when applying the adhesive to wounds on a joint like the elbow, which moves around a lot and would probably benefit from a looser bond, compared to a more static area of the body like the shin,” said co-first author Jianyu Li, Ph.D., a former Postdoctoral Fellow at the Wyss Institute who is now an Assistant Professor at McGill University.

The research team has also developed a computer simulation of AAD-assisted wound closure, which indicated that AAD could trigger human skin to contract at a speed similar to that of mouse skin, suggesting a greater probability of showing a clinical advantage to human patients.

“We are continuing this research with studies to learn more about how the mechanical cues exerted by AAD impact the biological process of wound healing, and how AAD performs across a range of different temperatures, as body temperature can vary at different locations,” said Benjamin Freedman. “We hope to pursue additional preclinical studies to demonstrate AAD’s potential as a medical product, and then work toward commercialization” added Freedman.

The research team also included Serena Blacklow, San Francisco, Mahdi Zeidi and Chao Chen. This research was supported by the National Institutes of Health, The Wyss Institute for Biologically Inspired Engineering at Harvard University, the National Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, and the Harvard University Materials Research Science and Engineering Center.